A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).

NCT04425538 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00000564
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.

Conditions

COVID-19

Keywords

COVID-19

Outcome Measures

Primary Outcomes (2)

• Time to Improvement in Oxygenation

  Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

  28 Days

• Number of p[Atients With Improvement in Oxygenation

  Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2)

  28 Days

Secondary Outcomes (14)

• 28-Day Survival Status

  28 Days

• Duration of Supplemental Oxygen Administration by Nasal Cannula

  28 Days

• Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula

  28 Days

• Number of Patients Requiring Mechanical Ventilation

  28 Days

• Number of Patients Requiring Vasopressor Support

  28 Days

Study Arms (1)

Infliximab

EXPERIMENTAL

All patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator.

Drug: Infliximab

Interventions

Infliximab DRUG

Either infliximab or infliximab-abda will be used at the discretion of the investigator

Also known as: infliximab-abda

Infliximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Able to provide informed consent
• Hospitalized adult patients with pneumonia evidenced by chest X-ray or CT scan
• Laboratory (RT-PCR) confirmed infection with 2019-nCoV or strongly suspected to be infected with SARS-COV2 with confirmation studies pending
• And at least one of the following:
• Respiratory frequency ≥30/min
• Blood oxygen saturation ≤93% on RA
• Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) \<300
• Worsening of lung involvement, defined as an increase in number and/or extension of pulmonary areas of consolidation, need for increased FiO2 to maintain stable O2 saturation, or worsening O2 saturation of \>3% with stable FiO2

You may not qualify if:

• Treatment with any TNFα inhibitor in the past 30 days
• Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 1000 mm3, hemoglobin \<8.0g/L, platelets \<50,000 per mm3, or AST or ALT greater than 5 x ULN
• Known active or latent Hepatitis B
• Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.
• Pregnancy
• Intubated for \>48hours
• Patients with uncontrolled systemic bacterial or fungal infections (Patients with a history of positive bacterial or fungal cultures but on enrollment are on appropriate therapy with negative repeat cultures may be enrolled)
• Serious co-morbidity, including:
• Myocardial infarction (within last month)
• Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV)
• Acute stroke (within last month)
• Uncontrolled malignancy
• Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) \< 30 ml /min/1.73 m\^2) at baseline

Sponsors & Collaborators

• Tufts Medical Center: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (2)

• Hachem H, Godara A, Schroeder C, Fein D, Mann H, Lawlor C, Marshall J, Klein A, Poutsiaka D, Breeze JL, Joshi R, Mathew P. Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-alpha antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure. medRxiv [Preprint]. 2021 Jun 2:2021.05.29.21258010. doi: 10.1101/2021.05.29.21258010.

  PMID: 34100026 RESULT

• Hachem H, Godara A, Schroeder C, Fein D, Mann H, Lawlor C, Marshall J, Klein A, Poutsiaka D, Breeze JL, Joshi R, Mathew P. Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFalpha-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure. J Clin Transl Sci. 2021 Jun 25;5(1):e146. doi: 10.1017/cts.2021.805. eCollection 2021.

  PMID: 34457357 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Neely Center for Clinical Research, Tufts Medical Center

ncccr@tuftsmedicalcenter.org

617-636-5000

Study Officials

• Paul Mathew, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 11, 2020
• Study Start: June 1, 2020
• Primary Completion: January 22, 2021
• Study Completion: January 22, 2021
• Last Updated: April 20, 2022
• Results First Posted: December 3, 2021

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)